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We must address the safety, security, and ethical issues of synthetic biology now, while the field is still in its infancy, for the following reasons:

Scientists will design and construct completely new biological systems and organisms not found in nature.

These novel systems and organisms will be created, in part, for practical purposes and applications.

New products of synthetic biology and related technologies could pose a variety of risks (some new, some familiar) to humans, animals, and the environment.

Synthetic biology has the potential to significantly impact our lives, and as a result, it is important that scientists, stakeholders, and the public engage in open discussions about the risks and benefits of these advances.

Synthetic biology (synbio) is an emerging field at the intersection of biology and engineering with the potential to no less than revolutionize the way we view and work with biotechnology today. By applying the toolbox of engineering disciplines to biology, an entirely new set of applications becomes possible. Potential benefits of synthetic biology include the development of low-cost drugs and the production of chemicals and energy by engineered bacteria. Nonetheless, potential and perceived risks due to deliberate or accidental damage are cause for concern. To ensure the vital and successful development of this new scientific field, it is necessary to be aware of these risks and devise possible biosafety strategies to minimize them.

Synthetic biology also poses ethical concerns that have only recently been explored by ethicists.1,2,3,4 The European SYNBIOSAFE research project, completed in 2008, was the first effort to focus specifically on the safety and ethical concerns of synthetic biology.5 However, additional studies need to be completed to facilitate the socially acceptable development of this science and its myriad applications.

What is synthetic biology?

Synthetic biology differs from genetic engineering because it involves the creation of new living systems.

Figure 1. Synthesis, transplantation, and booting of a synthetic genome in the bacteria Mycoplasma mycoides by the Craig Venter Institute. Source:“http://www.jcvi.org.

To understand synthetic biology, which is a combination of engineering and biological sciences, we need to know how it differs from traditional genetic engineering. Genetic engineering (also called recombinant DNA technology) is the manipulation of an organism’s genes, usually by transferring one gene from a donor organism to a host organism using a vector (a vehicle for the transfer). Synthetic biology, on the other hand, is the design and construction of completely novel biological systems not found in nature. In doing this, scientists hope to gain insights into living systems by re-constructing them on a much deeper, more detailed level than is possible using traditional genetic engineering techniques.

As a scientific label, synthetic biology currently encompasses many subfields and goals, including the following:5,6,7,8

Synthesizing DNA (chemically producing genetic code). Until recently, DNA could only be created by life itself, but now special DNA synthesis machines can actually “print” DNA to our specifications. For example, with this technology, scientists can download the genetic code of a virus and construct the DNA in a laboratory setting (see Figure 1).

Scientists use synthetic biology to understand how life is created and sustained.

Figure 2. A minimal organism is a life form that got rid of all genes that are not absolutely essential for surviving under special laboratory conditions. Source: SYNBIOSAFE DVD: http://www.synbiosafe.eu/DVD

Defining a minimal genome/minimal life. To create a minimal genome, scientists use bacteria that already have very small genomes and further reduce these bacteria until the organisms cannot survive any longer. One reason researchers do this is to determine the smallest possible genome that can sustain life (see Figure 2).

Engineering DNA-based biological circuits (i.e., biological parts, or bioparts). Instead of one gene, a whole system of several genes that interact with each other is transferred to a host organism. These systems, or circuits, are responsible for certain functions within the host organism, such as producing a specific protein or turning on/off a particular cellular function.

Figure 3. Protocell agents exhibit dynamic properties that are usually associated with living systems, such as movement and the production of structures. In these images, protocells are actively creating complex crystalline forms as they move around their environment. Some of these are remarkably similar to biological forms but have not been created by the action of DNA. Source: Rachel Armstrong: http://www.rachelarmstrong.me.

Xenobiology: creating biological systems based on biochemistry not found in nature. All forms of life on Earth are based on the DNA molecule. Now, scientists are constructing different molecules with similar functions (so-called xeno-nucleic acid [XNA])5 to build living systems that have never existed before (see Figure 4). This may be one way to avoid potential interference with naturally evolved DNA while working with biotechnology.

Out of the lab and into your life

The field of synthetic biology raises both new and existing concerns about potential impacts on society.

With its aim to transfer biology into technology, synthetic biology will have significant implications in our lives. On one hand, these implications deal with novel issues, different from those associated with other life science activities; on the other hand, we can expect to see the “old” issues resurface in new discussions. Although some of the topics have been debated for more than 35 years now (for example, during the famous Asilomar conference in 1975)10, one benefit of synthetic biology may be that long-standing issues are reconsidered in the light of this contemporary context.

Safety Considerations

Concerns exist about the accidental release of synthetic biology products into the environment.

Safety is a critical point that needs to be discussed up front to prevent unintentional exposure to pathogens, toxins, and otherwise potentially harmful biological material. Likewise, we need to protect humans, animals, and the environment from the accidental release of harmful synthetic biology agents. To maintain biotechnology at its current safety level, or even improve safety measures, we need to know the potential risks.

New methods in risk assessment. Researchers must decide whether a new synbio technique or application is safe enough (for human health, animals, and the environment) for use in restricted and less-restricted settings. The following examples of synbio products and technologies warrant a review and adaptation of current risk assessment practices:5,11-14

Newly created DNA-based systems and parts that are substantially different from existing life forms

Novel minimal life forms and whether they will survive in different environments

The potential infectious nature and survivability of newly created protocells

Exotic biological systems based on alternative biochemical structures (e.g., genetic code based on novel types of nucleotides, or an enlarged number of base pairs)
Synthetic biology, however, is not just about new risk. It is also about constructing new biological systems that make biology even safer to engineer. For this reason, researchers also need better safeguards.

Synthetic biology may help improve the safety of current biology practices and systems.

Synthetic biosafety systems. An important component of safety discussions is to explore how synthetic biology itself may overcome existing and possible future biosafety problems by contributing to the design of safer biosystems. For example, scientists might engineer and use biological systems based on alternative biochemical structures (like the XNA molecules mentioned previously) to avoid potential harm to existing life forms, such as gene flow between engineered organisms and wild species (see Figure 6).

Synthetic biology by amateur biologists and citizen scientists

One of the stated goals of synthetic biology is “to make biology easier to engineer.” In the words of physicist Freeman Dyson:15

Domesticated biotechnology, once it gets into the hands of housewives and >children, will give us an explosion of diversity of new living creatures, rather than >the monoculture crops that the big corporations prefer….The final step in the >domestication of biotechnology will be biotech games, designed like computer >games for children down to kindergarten age but played with real eggs and seeds >rather than with images on a screen….These games will be messy and possibly >dangerous. Rules and regulations will be needed to make sure that our kids do not >endanger themselves and others. The dangers of biotechnology are real and serious.
Careful attention must be paid to the way synthetic biology skills are disseminated among nonprofessionals (e.g., the do-it-yourself biology amateurs and biohackers), particularly in these areas:16,17

Care must be taken to ensure that everyone using synthetic biology resources does so safely and with sufficient awareness of, and training in, relevant biosafety techniques and approaches.

Proper mechanisms, such as laws, codes of conduct, voluntary measures, access restrictions to key materials, and reporting to institutional biosafety committees (IBCs), are in place to avoid unintentional harm.

We must be careful how synthetic biology skills and resources are used by non-professionals.

Security

Recent advances in DNA science have resulted in new biosecurity threats and concerns.

Biosecurity deals with the prevention of misuse through loss, theft, diversion, or intentional release of pathogens, toxins, and other biological materials. Biosecurity has been mostly absent from past discussions of the societal implications of the synthetic biology revolution. In recent years, however, technical advances in DNA synthesis have given rise to a completely new threat potential—namely, the synthesis of viruses without the need for a physical template. It is now possible for someone to use the genetic code of a potentially harmful virus, which can be found on the Internet with relative ease, to construct the virus in a lab. Scientists have also been able to generate viruses using DNA from previously infected cadavers, as was the case with the resurrected 1918 Spanish influenza virus.18 Given these possibilities, the issue of biosecurity is getting immediate attention and a suite of solutions has already been developed and implemented.19-21 Suggested solutions include the following:

Technical and regulatory checkpoints. DNA synthesis companies will need to check and screen orders to avoid the production of select agents, such as harmful viruses and bacterial DNA, as well as further develop and improve the technical means (e.g., software and databases) used to screen DNA orders.

Awareness. While biosecurity awareness among European DNA synthesis companies is relatively high, among most practicing life scientists it is comparatively low. Awareness needs to be enhanced through better communication and cooperation between the synthetic biology and biosecurity communities.

Education. Contemporary issues—such as past misuse of the life sciences for offensive bioweapon programs, the inadvertent results of security-related research, and the existence and operation of the Biological Weapons Convention22—should be systematically included in undergraduate and graduate biology curricula.

Governance and oversight. Addressing questions of governance and oversight of biosecurity will require more, and different, regulatory tools than are used when dealing with other societal issues. The involvement of all stakeholders is required to develop useful tools and avoid an oversight system with overly severe restrictions.

Ethical considerations

Synthetic biology raises ethical and moral questions about its products, processes, and applications.

Figure 5. A new chemical backbone for DNA creates a new tree of life that cannot exchange genetic information with the rest of the living world. Source: Schmidt 2010.

Whereas science and engineering mainly ask if we can do something, ethics asks whether we should do it. It is a question, therefore, about what is right or wrong with the standard procedures, applications, and distribution of synthetic biology, including the following:23-25

Designing and creating life. The goal of designing and creating new forms of life raises certain ethical questions related to the relationship between humans and other living organisms, as well as the moral status of the processes and products of synthetic biology. Along the same lines, further societal discussion is required about various conceptions of life, whether based on religious or humanistic grounds.

Risk-benefit distributions. An open and engaged ethical debate to address the moral acceptability of the risks is needed. In addition, the distribution of risks and benefits arising from various techniques and applications—in particular, those requiring the interaction of natural and synthetic organisms, as well as the implications of such interactions for human health, animal health, and the environment—must be discussed and clarified.

Benefits, access, and justice. Further discussion should be encouraged on the distribution of products and knowledge arising from synthetic biology research, including how they relate to various aspects of social justice, power relations, and the current global divide (e.g., impact on vulnerable people in the global south). Particular attention should be given to the debate about intellectual property rights and the effects of such rights on access to the products and knowledge of synthetic biology.

Science and society—moving forward

In the coming decades, synthetic biology may have a substantial impact on the world we live in. Given the scope of what synthetic biologists are trying to achieve, it is reasonable to start an early discourse about the technology, its applications, and the way we deal with it and its products. Few people outside the scientific community have heard of the field, but several projects have started to initiate a proactive discussion between science and society.5,24-26 To achieve the goal of making people aware of the many aspects and potential ramifications of synthetic biology, scientists and researchers must insist on the following:

Education. Topics related to synthetic biology, such as safety, security, and ethical issues, should be incorporated into the teaching curricula of synthetic biologists from the start of their education.

Public engagement and input from scientists and stakeholders are required to move forward.

Public engagement. As synthetic biology develops into applied technologies, it is important that scientists, stakeholders, and the public communicate in an interactive way. Past debates on genetic engineering suggest that, in order to prevent exaggerated hopes and fears, scientists should adopt an open approach toward the public. Both stakeholders and scientists should engage with members of the public in ethical discussions that go beyond mere campaigning or conveying information. In addition, different preferences and world-views associated with technology and innovation need to be addressed and not dismissed as unscientific.

Stakeholder involvement. Since developments in synthetic biology are so rapid, and regulation alone is no guarantee against misuse or societal controversies, it is necessary to involve relevant stakeholders in the decision-making process. This will allow for flexible and relatively swift ways of dealing with future problems through a combination of regulations, agreements, codes of conduct, and similar measures. This also requires a distribution of responsibilities. A multi-stakeholder approach for the governance of synthetic biology and its applications should involve scientists, regulators, members of civil society, industry representatives, philosophers, and other relevant groups.

Synthetic biology is an exciting new science and engineering field brimming with possibilities and potential, but we need to ensure this new science is utilized in a responsible and ethical manner. As a society, we will no doubt embrace many of the field’s new methods, techniques, and applications, but we may also reject some if they do not meet our agreed-upon criteria of security, safety, or ethical acceptability. To ensure our decisions in this regard are both responsible and informed, it is crucial that scientists, stakeholders, and members of the public work together to develop a solid framework that guides us in this complex decision-making process.

Markus Schmidt has an educational background in electronic engineering, biology, and ecological risk assessment. His research interests include biosafety and technology assessment of novel biotechnologies, including synthetic biology, management of genetic resources, public perception, science communication, and filmmaking. Schmidt coordinated and participated in several European Commission FP6 and FP7 research projects, edited a book on synthetic biology, and guest edited a special issue on societal aspects of synthetic biology. Schmidt works for the Biosafety Working Group, Organisation for International Dialogue and Conflict Management (IDC), Vienna, Austria.
http://www.synbiosafe.euhttp://www.idialog.eu

SYNBIOSAFE Documentary

Extreme Engineering: An Introduction to Synthetic Biology

“Genetic engineering is passé. Today, scientists aren’t just mapping genomes and manipulating genes, they’re building life from scratch—and they’re doing it in the absence of societal debate and regulatory oversight.” Read more from this interesting synbio introduction by the ETC Group, Canada.
http://www.etcgroup.org/upload/publication/602/01/synbioreportweb.pdf

getinvolved links

Join the discussion about safety of synthetic biology

SYNBIOSAFE was the first scientific project in Europe to bring attention to the safety concerns and ethical considerations of synthetic biology. Visit their website to learn more about SYNBIO projects, post to the discussion forum, or watch interviews with experts in the field.
http://www.synbiosafe.eu/

educatorresources

Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

Ethics Primer
The Ethics Primer provides engaging, interactive, and classroom-friendly lesson ideas for integrating ethical issues into a science classroom. It also provides basic background on ethics as a discipline, with straightforward descriptions of major ethical theories. Several decision-making frameworks are included to help students apply reasoned analysis to ethical issues.
http://www.nwabr.org/curriculum/ethics-primerBioethics 101
Bioethics 101 provides a systematic, five-lesson introductory course to support educators in incorporating bioethics into the classroom through the use of sequential, day-to-day lesson plans. This curriculum is designed to help science teachers in guiding their students to analyze issues using scientific facts, ethical principles, and reasoned judgment.
http://www.nwabr.org/curriculum/bioethics-101Advanced Bioinformatics: Genetic Research
This curriculum unit explores how bioinformatics is used to perform genetic research. Students examine DNA sequences from different animal species, investigate the relationship between protein structure and function, and explore evolutionary relationships among eukaryotic organisms. Throughout the unit, students are presented with a number of career options in which the tools of bioinformatics are developed or used.
http://www.nwabr.org/curriculum/advanced-bioinformatics-genetic-research

Freeman Dyson has spent most of his life as a professor of physics at the Institute for Advanced Study in Princeton. This quote is from Dyson, F. 2007, July 19. Our Biotech Future. The New York Review of Books 54 (12). See: http://www.nybooks.com/articles/20370 (accessed October 8, 2010).

To obtain the code of the 1918 influenza virus, researchers exhumed long-frozen corpses (of people who died of that disease at the end of World War I) from permafrost soils in Alaska, Russia, and Norway. They then removed lung tissue from the corpses and isolated pieces of the virus. After having obtained the DNA information, they synthesised the virus de novo in the lab.

The Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction—more commonly known as the Biological and Toxin Weapons Convention (BTWC)—was simultaneously opened for signature in Moscow, Washington, and London on 10 April 1972 and entered into force on 26 March 1975.
UK, US, and Soviet Governments. 1975. Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction.http://www.opbw.org/convention/documents/btwctext.pdf (accessed December 30, 2010).